| Literature DB >> 33230297 |
Alice Lepelley1, Marine Depp2, Andrew P Badrock2, Carolina Uggenti2, Mathieu P Rodero1, Marie-Thérèse El-Daher2, Gillian I Rice3, Somdutta Dhir2, Ann P Wheeler4, Ashish Dhir2, Waad Albawardi4, Marie-Louise Frémond1, Luis Seabra1, Jennifer Doig2, Natalie Blair2, Maria José Martin-Niclos1, Erika Della Mina1, Alejandro Rubio-Roldán5, Jose L García-Pérez4,5, Duncan Sproul4,6, Jan Rehwinkel7, Jonny Hertzog7, Anne Boland-Auge8, Robert Olaso8, Jean-François Deleuze8, Julien Baruteau9, Karine Brochard10, Jonathan Buckley11, Vanessa Cavallera12, Cristina Cereda13, Liesbeth M H De Waele14, Angus Dobbie15, Diane Doummar16, Frances Elmslie17, Margarete Koch-Hogrebe18, Ram Kumar19, Kate Lamb20, John H Livingston21, Anirban Majumdar22, Charles Marques Lorenço23, Simona Orcesi12,24, Sylviane Peudenier25, Kevin Rostasy18, Caroline A Salmon26, Christiaan Scott27, Davide Tonduti28, Guy Touati29, Marialuisa Valente13, Hélio van der Linden30, Hilde Van Esch31, Marie Vermelle32, Kate Webb27, Andrew P Jackson4, Martin A M Reijns4, Nick Gilbert4, Yanick J Crow33,34.
Abstract
Inappropriate stimulation or defective negative regulation of the type I interferon response can lead to autoinflammation. In genetically uncharacterized cases of the type I interferonopathy Aicardi-Goutières syndrome, we identified biallelic mutations in LSM11 and RNU7-1, which encode components of the replication-dependent histone pre-mRNA-processing complex. Mutations were associated with the misprocessing of canonical histone transcripts and a disturbance of linker histone stoichiometry. Additionally, we observed an altered distribution of nuclear cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS) and enhanced interferon signaling mediated by the cGAS-stimulator of interferon genes (STING) pathway in patient-derived fibroblasts. Finally, we established that chromatin without linker histone stimulates cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) production in vitro more efficiently. We conclude that nuclear histones, as key constituents of chromatin, are essential in suppressing the immunogenicity of self-DNA.Entities:
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Year: 2020 PMID： 33230297 DOI： 10.1038/s41588-020-00737-3
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330